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Abstract：
Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.
摘要：
宫颈癌（CC）是女性中第四大癌症，是主要的妇科恶性肿瘤之一。在肿瘤微环境中，癌症相关成纤维细胞（CAFs）在恶性进展过程中发挥关键作用，表现出多种异质表型。CAFs表达表型标记，如成纤维细胞活化蛋白（FAP），波形蛋白,S100A4,α-平滑肌肌动蛋白(αSMA),和功能标记如MMP9。本研究旨在评估波形蛋白的蛋白表达，S100A4,αSMA,FAP,间充质干细胞（MSC）-CAF细胞中的MMP9，以及宫颈癌样本。用HeLa和SiHa肿瘤细胞上清液刺激MSC细胞，然后进行蛋白质评估和细胞因子谱以确认分化为CAF表型。此外,进行自动免疫组织化学(IHQa)以评估这些蛋白在不同阶段的CC样品中的表达。我们的发现揭示了FAP在刺激的MSC细胞中的高表达,伴随着促炎/抗炎细胞因子的分泌。另一方面,观察到CC样品具有高表达的FAP,波形蛋白,αSMA,MMP9最重要的是,在不同阶段，其激活蛋白αSMA和FAP的高表达。在早期阶段,成肌纤维细胞样表型（CAFsαSMA+FAP+），并且在晚期阶段为原瘤表型（CAFαSMA-FAP）。总之,FAP在宫颈癌进展过程中对CAFs的激活具有关键作用。
